Cbmt-03. a Novel Metabolic Pet Tracer Strategy to Determine Early Effects of Tumor Treating Fields (ttfields)
Year: 2018
Type: article
Abstract: Pyruvate kinase M2 (PKM2) is a key marker of cancer metabolic reprogramming since it catalyzes the final step in glycolysis. [18F]DASA-23 is a novel radiotracer that measures aberrantly-expressed PKM2 in glioblastoma (GBM). Tumor treating fields (TTFields), the application of alternating electric fields (100–300 kHz, 1–4 V/cm) to tumors, is emerging as the fourth therapeutic modality in GBM after surgery, temozolomide (TMZ) chemotherapy, and radiotherapy. There is an important need to assess early on whether a patient’s GBM is responding to a given therapy. We evaluated the ability of [18F]DASA-23 to detect changes in GBM metabolism in response to standard-of-care (TMZ) and emerging (TTFields) therapies. Human U87 GBM cells were subjected to 200 kHz TTFields, the IC50 of TMZ, or vehicle for three or six days (n≥3/condition), followed by evaluation of [18F]DASA-23 uptake. Immunofluorescence for PKM2 was performed to confirm the [18F]DASA-23 uptake results. Finally, Western blot analysis was performed to determine the effect of TMZ and TTFields exposure on the expression of PKM2 and a downstream enzyme, lactate dehydrogenase (LDH). 2-way ANOVA with multiple comparisons was performed. Data are reported as mean±SD. There was a significant interaction between the treatment (TTFields, TMZ, or vehicle) and treatment duration (3 or 6 days) on PKM2 expression as measured by [18F]DASA-23 uptake (p=0.005) at 30 minutes post-addition of radioactivity. Immunofluorescence independently confirmed reduced PKM2 expression due to TTFields. Western blot analysis revealed reduced PKM2 and LDH (normalized to loading control) without/with TMZ (0.43 ± 0.13 vs. 0.30 ± 0.05 [p=0.14] and 0.61 ± 0.16 vs. 0.43 ± 0.04 [p=0.12], respectively) and without/with TTFields (0.70 ± 0.23 vs. 0.15 ± 0.09 [p=0.01] and 1.14 ± 0.36 vs. 0.54 ± 0.14 [p=0.04], respectively). These data highlight the potential for non-invasive assessment of GBM’s glycolytic response to standard and emerging therapies using [18F]DASA-23. A clinical study is underway to evaluate the ability of [18F]DASA-23 to predict responders vs. non-responders to anti-GBM therapy.
Source: Neuro-Oncology
Institutions: Stanford Medicine, Stanford University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2899666281